PMID- 33643689 OWN - NLM STAT- MEDLINE DCOM- 20210728 LR - 20220531 IS - 2162-402X (Electronic) IS - 2162-4011 (Print) IS - 2162-4011 (Linking) VI - 10 IP - 1 DP - 2021 Jan 31 TI - A stratified phase I dose escalation trial of hypofractionated radiotherapy followed by ipilimumab in metastatic melanoma: long-term follow-up and final outcomes. PG - 1863631 LID - 10.1080/2162402X.2020.1863631 [doi] LID - 1863631 AB - We conducted a phase I dose-escalation trial of radiation with ipilimumab in patients with melanoma with >/=2 metastatic lesions. Here, we report the final full clinical analysis. Patients received RT (6 or 8 Gy x 2 or 3 doses) to a single lesion followed by 4 cycles of ipilimumab. The primary endpoint was maximum tolerated dose of RT, and secondary endpoint was response at non-radiated sites. Twenty-two patients with treatment-naive (n = 11) or treatment-refractory (n = 11) Stage IV melanoma were enrolled. There were 31 treatment-related adverse events (AEs), of which 16 were deemed immune-related. Eleven patients had grade 3 AEs (no grade 4/5). There were no dose-limiting toxicities related to the radiation/ipilimumab combination. Five of 22 patients (22.7%, 95% CI 7.8-45.4%) had partial response as best response and three (13.6%) had stable disease. Median overall survival was 10.7 months (95% CI, 4.9 months to not-estimable) and median progression-free survival 3.6 months (95% CI, 2.9 months to 7.8 months). Seven patients were still alive at the time of last follow-up (median follow-up 89.2 months), most of whom received pembrolizumab after progression. Radiotherapy followed by ipilimumab was well tolerated and yielded a response rate that compares favorably to the objective response rate with ipilimumab alone. Furthermore, 32% of patients are long-term survivors, most of whom received pembrolizumab. Based on these results, the recommended dose that was used in subsequent Phase 2 trials was 8 Gy x 3 doses. Clinical Trial Registration: NCT01497808 (www.clinicaltrials.gov). CI - (c) 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. FAU - Maity, Amit AU - Maity A AD - Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. FAU - Mick, Rosemarie AU - Mick R AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. AD - Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. FAU - Rengan, Ramesh AU - Rengan R AD - Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA. FAU - Mitchell, Tara C AU - Mitchell TC AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Amaravadi, Ravi K AU - Amaravadi RK AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Schuchter, Lynn M AU - Schuchter LM AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Pryma, Daniel A AU - Pryma DA AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. FAU - Patsch, Dana M AU - Patsch DM AD - Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Maity, Alisha P AU - Maity AP AD - Department of Medicine, Lankenau Medical Center, Wynnewood, PA, USA. FAU - Minn, Andy J AU - Minn AJ AD - Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. AD - Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. AD - Institute for Immunology, University of Pennsylvania, Philadelphia, PA, USA. AD - Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation, University of Pennsylvania, Philadelphia, PA, USA. FAU - Vonderheide, Robert H AU - Vonderheide RH AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. AD - Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Lukens, John N AU - Lukens JN AD - Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. AD - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. LA - eng SI - ClinicalTrials.gov/NCT01497808 GR - P01 CA210944/CA/NCI NIH HHS/United States GR - P30 CA016520/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210131 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 RN - 0 (Ipilimumab) SB - IM MH - Follow-Up Studies MH - Humans MH - Ipilimumab/therapeutic use MH - *Melanoma/drug therapy MH - *Neoplasms, Second Primary MH - Progression-Free Survival PMC - PMC7872096 OTO - NOTNLM OT - CTLA-4 OT - abscopal OT - hypofractionated radiation OT - ipilimumab OT - radiation EDAT- 2021/03/02 06:00 MHDA- 2021/07/29 06:00 PMCR- 2021/01/31 CRDT- 2021/03/01 05:38 PHST- 2021/03/01 05:38 [entrez] PHST- 2021/03/02 06:00 [pubmed] PHST- 2021/07/29 06:00 [medline] PHST- 2021/01/31 00:00 [pmc-release] AID - 1863631 [pii] AID - 10.1080/2162402X.2020.1863631 [doi] PST - epublish SO - Oncoimmunology. 2021 Jan 31;10(1):1863631. doi: 10.1080/2162402X.2020.1863631.